As one of just a few interventional radiologists with their own
vascular biology lab in North America, Dr. Misra is excited and proudly uses
his research to help patients.

"In my practice, my research is very relevant to the
patient and improving therapeutic outcomes, so what we employ in our lab is a
combination of animal models and biology to understand how to improve the
procedures we are doing currently," Dr. Misra says.

An area of focus for Dr. Misra has been renal disease, where he has sought to understand why arteriovenous fistulas and grafts, used for providing patients with vascular access for hemodialysis, develop stenosis and fail.

About 700,000 patients in the United States have end-stage renal disease and the majority of them require hemodialysis for the purification of their blood. A well-functioning hemodialysis arteriovenous fistula is the preferred vascular access. Currently, the average patency of these arteriovenous fistulas is 60 percent in one year. In order to maintain patency, angioplasty is the preferred endovascular technique and its patency at one year is only 50 to 70 percent. There are no effective therapies to prevent blockages from occurring in arteriovenous fistulas.

Fat-derived mesenchymal stem cells

Dr. Misra initially researched the failure of surgical
fistula placement, which led to an investigation into why angioplasty does not
work well when treating fistula failures.

Dr. Misra and his colleagues created animal models to
understand the biology of arteriovenous fistula failures. They combined this
with cell culture experiments, and his team learned that this set of "biological
tools" could be used in other areas — such as with kidney injury caused by
the use of iodinated contrast administration into the blood vessel and understanding
why vascular malformations form.

Since the start of the lab, Dr. Misra and his colleagues
have been conducting studies to create therapies to improve the outcomes of current
procedures.

"There are several things I consider when thinking
about this problem. One, I try to look at, how can we design a therapy that
interventional radiologists, surgeons, cardiologists, and other proceduralists would
want to use every day?" Dr. Misra says. "Number two, can we design a
therapy that can improve our procedural outcomes beyond what we’re getting
today? And number three, can we design something that will work in the next five
years that we can test in humans in a phase 1 clinical trial?"

Through their stem cell research, Dr. Misra and his
colleagues began a first-of-its-kind phase 1 human clinical trial with about two
dozen patients to test whether a patient’s own stem cells isolated from fat can
prevent venous stenosis formation. Dr. Misra calls this one of his proudest
achievements.

Along with improving procedural outcomes, Dr. Misra and his
colleagues are in the process of exploring and improving drug therapies.

In the lab, Dr. Misra and his colleagues discovered an
orphan drug, calcitriol tagged to nanoparticles composed of bio-absorbable poly
lactic-co-glycolic acid (PLGA) that inhibits stenosis formation in dialysis
arteriovenous fistulas. The drug is part of a National Institutes of Health grant
and was recently issued a method patent. This was the lab’s second patent.

Another therapy in development is an orphan drug that
prevents kidney injury in animal models if given before iodinated contrast administration.

"Science is a team sport. I think being at a place like Mayo allows you to tap into other parts of the team."

Sanjay Misra, M.D.

Aside from renal disease, the lab also studies a rare condition where malformations, called hereditary hemorrhagic telangiectasia, form in patients. In patients with this condition, pulmonary artery to vein malformations occur which can lead to hypoxia, stroke, heart failure and other problems. These are treated with embolization, in which platinum coils are deposited to stop the malformation from growing or rupturing. Dr. Misra and his colleagues aim to understand the biology of malformations associated with hereditary hemorrhagic telangiectasia to improve embolization treatment outcomes using adjunctive drug therapies. About 20 percent of these patients require multiple procedures to close the malformations.

"That’s sort of what’s different from my lab compared
to an imaging lab — we try to understand why our current interventions and
procedures do not work well and try to improve these therapies by combining
with drugs, cells, or other biologics in a way that we can help our patients in
a short period of time," Dr. Misra says.

The lab also allows Dr. Misra opportunities to mentor young
staff, some of whom have gone on to receive grants of their own and become assistant
or associate professors.

"Mentoring young trainees and staff is very exciting
and fulfilling at the same time," he says. "Helping them succeed is important
in helping develop the next generation of biomedical workforce so that we can improve
our knowledge and understanding of human disease."

The work of the Vascular and Interventional Radiology
Translational Research Lab is made possible because of grant funding and
supporters outside of the lab, Dr. Misra says.

"Science is a team sport. I think being at a place like
Mayo allows you to tap into other parts of the team," he adds. "We work
in a very team-oriented way. We work with surgeons, kidney doctors, basic
scientists, drug delivery people, also people not at Mayo. I think you need to
have a really broad perspective when you’re thinking about this.